The overall objective of this project is to further refine the use of the 6-14C-arginine (arg) pulse labeling technique in the study of human and murine plasma cell neoplasms and to identify and understand the inter-relationship between tumor cell-host factors and the effect of treatment on M component biosynthesis. During this period (November 1979 to November 1980), our approach has been to further study the LPC-1 murine plasmacytoma tumor cell subcompartments by various physical fractionation techniques (e.g., two step Ficoll-Hypaque fractionation) and to characterize the resultant fractions by a number of techniques including DNA synthesis, DNA content, tumorigenicity, clonogenicity, M component biosynthesis and sensitivity to various treatment modalities. Heterogeneity of the LPC-1 tumor line has been demonstrated by tumor cell morphology (lymphoid/plasmacytoid), DNA content (diploid/approximately tetraploid) and by producing a cyclophosphamide resistant subline (CY-R) by means of selection pressure with subcurative doses of CY. Preliminary study of the differences between the sensitive parent (CY-S) and the CY-R subline have been undertaken in order to understand the nature of this acquired cyclophosphamide resistance. Current plans include further characterization of the subcompartments of the LPC-1 tumor with physical isolation of the plasmacytoid fraction in order to study intercompartment cellular traffic. We will also further characterize the CY-R subline. These various tumor fractions and sublines will be studied in vivo as well as in vitro by use of the 6-14C-arg pulse labeling technique.